Acetic Acid → N-(4-(2,4-difluorophenoxy)phenyl)-1-pyrid-3-ylethylamine

HRID 392418Notes

Reaction equation

HRID 392418 reaction equation
[F:1][C:2]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][CH:6]=1.[C:17]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)(=O)[CH3:18].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[F:1][C:2]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([NH:11][CH:17]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH3:18])=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 95893-AcetylpyridineHCID 5049666Sodium triacetoxyborohydrideHCID 226635574-(2,4-Difluorophenoxy)aniline

Product 1

HCID 22663571N-(4-(2,4-difluorophenoxy)phenyl)-1-pyrid-3-ylethylamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-(4-(2,4-difluorophenoxy)phenyl)amine (1.0 equiv.) in dichloromethane (0.2 M) was cooled to 0° C. and treated with 3-acetylpyridine (Aldrich; 1.4 equiv.), acetic acid (5.0 equiv.), and sodium triacetoxyborohydride (2.5 equiv.). The reaction was allowed to warm to ambient temperature and stirred an additional 22 hours. The reaction was cautiously quenched with saturated aqueous NaHCO3 then adjusted to pH=10 with 1 N NaOH. The mixture was stirred for 4 hours then the layers were separated. The aqueous layer was extracted twice with DCM. The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude material was purified via radial chromatography eluting with 50:50 to 60:40 ethyl acetate/hexanes to give N-(4-(2,4-difluorophenoxy)phenyl)-1-pyrid-3-ylethylamine. 1H NMR (400 MHz) 1.54 (3H, d, J=6.7 Hz), 3.96 (1H, bs), 4.48 (1H, q, J=6.7 Hz), 6.44 (2H, m), 6.76 (2H, m), 6.83-6.93 (2H, m), 7.24 (1H, m), 7.44 (1H, m), 7.68 (1H, td, J=1.8, 7.9 Hz), 8.50 (1H, d, J=3.8 Hz), 8.64 (1H, bs). HRMS calcd 327.1309. Found 327.1308.

Workup

  1. customThe reaction was cautiously quenched with saturated aqueous NaHCO3
  2. stirringThe mixture was stirred for 4 hours
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with DCM
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified via radial chromatography
  10. washeluting with 50:50 to 60:40 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9fee0f34290d4c48a68ba7b574478175
Source dataset
uspto-grants-2004_10
Patent number
US06800651B2

Reaction notes

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